Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-α2a (IFN) in metastatic renal cell carcinoma (mRCC)

Abstract

5020 Background: In the AVOREN trial, BEV (Avastin) + IFN significantly improved PFS and ORR compared with placebo + IFN in pts with mRCC [Escudier, Lancet. 2007]. The study was unblinded after interim analysis due to significant superiority of BEV + IFN and the DSMB recommended crossover of pts from placebo to BEV (n = 13). We report here the results of the final analysis. Methods: Eligible pts had predominantly clear-cell mRCC, prior nephrectomy, no prior systemic therapy for metastatic disease, KPS ≥70%, no CNS metastases and adequate organ function. Pts were randomised to IFN (9MIU tiw) + BEV (10 mg/kg q2w) or placebo until disease progression. Primary endpoint was OS, with pre-planned stratified and unstratified analyses according to regional regulatory requirements. Results: 649 pts were randomised to BEV + IFN (n = 327) or placebo + IFN (n = 322). An independent radiological review confirmed previous investigator assessments, showing PFS of 10.4 vs 5.5 months (HR 0.57) and a response rate of 31% vs 12% in the two arms, verifying the robustness of the investigator analysis. At the time of final OS analysis (444 events), median follow-up was 22.9 months in the BEV arm and 20.6 months in the placebo arm. Final median OS stratified for region and Motzer score was 23.3 months in the BEV + IFN arm and 21.3 months in the IFN + placebo arm (HR 0.86 [95% CI: 0.72–1.04], p = 0.1291). No new or unexpected AEs were observed. More pts in the IFN + placebo arm than the BEV + IFN arm received post-protocol therapy, including TKIs, mTOR inhibitors, cytokines and chemotherapy: 180 (55%) in the BEV + IFN arm and 202 (63%) in the IFN + placebo arm. Exploratory analysis showed that median OS in pts receiving second-line TKI therapy (BEV + IFN, n = 96; IFN + placebo, n = 81) was 38.6 months vs 33.2 months (HR = 0.77 [95% CI: 0.51–1.15], p = 0.1948). Further subgroup analyses will be presented. Conclusions: BEV + IFN is a first-line standard of care for pts with mRCC, improving PFS and ORR, with a trend toward improved OS, compared with IFN. The observed OS results may have been influenced by subsequent anti-neoplastic therapy, which was not prespecified in the protocol and represents an uncontrolled element of the OS analysis. [Table: see text]